rs10495751

Positions:

• chr2-25093176-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014971.2(EFR3B):​c.212+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,544,070 control chromosomes in the GnomAD database, including 5,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (2373 hom., cov: 32)
  • Exomes 𝑓: 0.037 (2654 hom.)
• Consequence: EFR3B NM_014971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604

Genes affected

EFR3B (HGNC:29155): (EFR3 homolog B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFR3B	NM_014971.2	c.212+46T>C		intron_variant		ENST00000403714.8	NP_055786.1
EFR3B	NM_001319099.2	c.107+46T>C		intron_variant			NP_001306028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFR3B	ENST00000403714.8	c.212+46T>C		intron_variant		5	NM_014971.2	ENSP00000384081	P1
EFR3B	ENST00000401432.7	c.212+46T>C		intron_variant		2		ENSP00000386082
EFR3B	ENST00000402191.5	c.107+46T>C		intron_variant		5		ENSP00000385832

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17079 AN: 152018 Hom.: 2365 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0410

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0833

GnomAD3 exomes AF: 0.0475 AC: 7355 AN: 154774 Hom.: 590 AF XY: 0.0452 AC XY: 3686 AN XY: 81540

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.0262

Gnomad ASJ exome AF: 0.0472

Gnomad EAS exome AF: 0.000461

Gnomad SAS exome AF: 0.0560

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.0285

Gnomad OTH exome AF: 0.0395

GnomAD4 exome AF: 0.0372 AC: 51748 AN: 1391934 Hom.: 2654 Cov.: 30 AF XY: 0.0369 AC XY: 25328 AN XY: 685742

Gnomad4 AFR exome AF: 0.347

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.0462

Gnomad4 EAS exome AF: 0.000337

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.0282

Gnomad4 OTH exome AF: 0.0499

GnomAD4 genome AF: 0.112 AC: 17102 AN: 152136 Hom.: 2373 Cov.: 32 AF XY: 0.108 AC XY: 8072 AN XY: 74400

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0410

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0382 Hom.: 677

Bravo AF: 0.126

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10495751; hg19: chr2-25316045;